Posts in grid advice needed

Hello all.

I’m trying to achieve a grid of WordPress posts looking something like this: http://imgur.com/i42g3MV , i.e. a bunch of different sized boxes with different kinds of content. Not really sure how to approach this.

The client is not yet sure exactly what kind of content will be on the page, and it must be user-friendly. Also, I’m trying to stay away from premium jquery plugins as much as possible.

Making columns together with post formats (large post, regular post, semi-small post, small post) feels kind of messy in the admin area and will require alot of querying, getting the 1/2/3 latest of each post format, am I right?

Any advice would be greatly appreciated.
Thanks